Frequency Of Chromosome 22q11.2 Microdeletion In Sporadic Non-syndromic Conotruncal Heart Defects By Multiplex Ligation-dependent Probe Amplification

OBJECTIVESThe aim of this study was to evaluate MLPA assay of detection of chromosome 22q11.2 microdeletion, and to investigate the frequency of 22q11.2 deletion in patients with non-syndromic CTDs at a Department of Pediatric Thoracic and Cardiovascular Surgery.METHODSBetween March 2008 and September 2009, thirty-two patients (sixteen male; 16 female;mean age,3.6±3.1 years, range 1-13 years) were selected and evaluated by history, physical examination and medical records in our department. Of these patients, sixteen patients who were previous diagnostic of a 22q11.2 microdeletion were in positive control group; while, the other 16 healthy children were in negative control group. All the patients were detected by MLPA and FISH for the presence of a 22q11.2 microdeletion after informed consent. Diagnostic efficacy was assessed by sensitivity, specificity and Kappa analysis.Seventy-seven non-syndromic CTD children (42 male,35 female, aged 0-10 years) were selected and evaluated by history, physical examination and review of medical records. Peripheral blood was drawn for genomic DNA after informed consent; chromosome 22q11.2 microdeletion was screened by Multiplex Ligation-dependent Probe Amplification (MLPA) and demonstrated by Fluorescence in situ hybridization (FISH). Genotype-phenotype correlations were performed using Fishers exact test. P values less than 0.05 on a 2-sided test were considered significant.RESULTSWe have applied theses two assays of detection of chromosome 22q11.2 microdeletion in a group of 32 patients.16 patients in positive control group were found to have a 22qll.2 deletion and, whose deletion size was a 3-Mb segment. However, chromosome 22q11.2 deletion was not found in negative control group. The MLPA results were in agreement with the Fish's. Therefore, it was high in both of MLPA's sensitivity and specificity.We evaluated 77 non-syndromic CTD patients for a 22q11.2 deletion.55 patients presented tetralogy of fallot (TOF),4 patients presented pulmonary atresia with ventricular septal defect (PA-VSD),8 patients presented double outlet right ventricle (DORV) and 10 patients presented transposition of the great arteries (TGA). Six children (7.8%) were found to have a del22q; four presented TOF, one presented DORV and one presented PA-VSD. Interestingly, none of the ten TGA children had a deletion.CONCLUSIONS1. MLPA is a rapid, reliable, high-throughput and relative economical alternative to FISH technology for the diagnosis of a 22qll.2 microdeletion. It can provide reliable and helpful information for clinical diagnosis of 22q11.2 microdeletion syndrome.2. Chromosome 22q11.2 microdeletion in non-syndromic CTD children is present in approximately 7.8% of individuals. We suggest a tendency towards a higher prevalence of PA-VSD, DORV and TOF in non-syndromic CTD patients with 22q11.2 microdeletion. Molecular genetic screening of non-syndromic CTD children may be important for the correct care of these children and a more specific genetic diagnostic and counselling.